NCT-58

NCT-58 is a potent inhibitor of C-terminal HSP90. NCT-58 does not induce the heat shock response (HSR) due to its targeting of the C-terminal region and elicits anti-tumor activity via the simultaneous downregulation of HER family members as well as inhibition of Akt phosphorylation. NCT-58 kills Trastuzumab-resistant breast cancer stem-like cells. NCT-58 induces apoptosis in HER2-positive breast cancer cells[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HSP

Signaling Pathways >> Cell Cycle/DNA Damage >> HSP

HSP90

Apoptosis

NCT-58 treatment (0.1-20 μM; 72 hours) dose-dependently reduces cell viability in HER2-positive BT474 and SKBR3 cells[1]. NCT-58 treatment (0.1-10 μM; 72 hours) increases the number of early and late apoptotic cells in HER2-positive BT474 and SKBR3 cells[1]. NCT-58 treatment (2-10 μM; 72 hours) effectively reduced the levels of truncated p95HER2 and its phosphorylated form, as well as downregulation of Akt and phospho-Akt (Ser473) protein contents in JIMT-1 and MDA-MB-453 cells[1]. Cell Viability Assay[1] Cell Line: BT474 and SKBR3 cells Concentration: 0, 0.1, 0.5, 1, 5, 10, 15, 20 μM Incubation Time: 72 hours Result: Significantly reduced cell growth. Apoptosis Analysis[1] Cell Line: BT474 and SKBR3 cells Concentration: 0, 2, 10 μM Incubation Time: 72 hours Result: Increased the number of early and late apoptotic cells. Western Blot Analysis[1] Cell Line: Trastuzumab-resistant JIMT-1 and MDA-MB-453 cells Concentration: 0, 2, 10 μM Incubation Time: 72 hours Result: Effectively reduced the levels of truncated p95HER2 and its phosphorylated form, as well as downregulation of Akt and phospho-Akt (Ser473) protein contents in JIMT-1 and MDA-MB-453 cells.

NCT-58 (30 mg/kg; i.p.; every other day for 47 days) suppresses Trastuzumab-resistant tumor growth[1]. NCT-58 (30 mg/kg; i.p.; every other day for 47 days) causes a significant impediment of tumor growth and a marked decrease in tumor weight[1]. Animal Model: Trastuzumab-resistant xenograft model (female nude mice; 6 weeks; BALB/c)[1] Dosage: 30 mg/kg Administration: i.p.; every other day for 47 days Result: Significantly reduced tumor growth.

[1]. Park S, et al. The C-terminal HSP90 inhibitor NCT-58 kills trastuzumab-resistant breast cancer stem-like cells. Cell Death Discov. 2021;7(1):354.